Tumors develop when, in a healthy organ, cells display uncontrolled growth and division beyond the normal limits and escape cell death mechanisms.
Viruses are masters for manipulating the proliferation or death of the host cell they infect, mainly by interfering with crucial endogenous interactions. Rabies virus (RABV) is a neurotropic virus, which causes fatal encephalitis in mammals. RABV has developed a particular strategy to ensure its propagation in the nervous system. Its virulence correlates with the ability of infected neurons to survive.
Virulent RABV strains have been described to preserve the integrity of the neuronal network, thereby favoring the spreading of the virulent strain within the Central Nervous System (CNS), although they have also been described to have no positive or a negative impact on neurite outgrowth, for example no positive or a negative impact on axon outgrowth of rat motoneurons in culture (Guigoni and Coulon, 2002).
Attenuation of laboratory strains in the search for candidate live anti-RABV vaccines led to the observation that RABV attenuation is linked to their ability to trigger cell death. WO 03/048198 relates to the G protein of RABV and to fragments thereof of at least 100 amino acids, which induce the disruption of the neuronal cell integrity and the formation of apoptotic bodies. WO 03/048198 describes that the effect of these apoptotic bodies is to stimulate a humoral immune response, preferably a B-dependent humoral immune response.
Préhaud et al., 2010 have described that the various partners of attenuated rabies virus strains include PTPN4, MAST2, MAST1, DLG2, MDPZ. A cell—penetrating peptide (Cyto13-att; SEQ ID NO: 11) encoding the PDZ binding site (PDZ-BS) of the attenuated ERA rabies virus strain induces cell death in the neuroblastoma cell line SK-N-SH, whereas peptides from the virulent VIR strain PDZ-BS (Cyto13-vir; SEQ ID NO: 14) or peptides lacking the last four amino acids (Cyto9-Δ; SEQ ID NO: 17) do not (Préhaud et al., 2010).